The present invention relates to a novel renin-active substance which exhibits enzymatic activity or, namely, renin activity as a combination of the human prorenin with an anti-peptide-specific antibody capable of forming an immunocomplex by combining with the profragment peptide of human prorenin.
Prorenin is produced mainly in the kidney as a precursor of the completely matured renin or, namely, as the completely matured renin having a profragment with a sequence of 43 amino acid residues combined at the N-terminal thereof and released into blood.
While the concentration of this prorenin in blood is about 10 times higher than the completely matured renin, the prorenin per se does not exhibit any enzymatic activity so that it is a conventional practice to convert the same into the completely matured renin by decoupling the profragment portion with a protease such as trypsin and pepsin.
Non-enzymatic methods were also proposed some years ago. For example, a method is proposed for activation at a low temperature in an acidic condition without alteration in the primary structure in Nature, volume 288, pages 702-705 (1980), Journal of Biological Chemistry, volume 262, pages 2472-2477 (1987), Clinical Chemistry, volume 37, pages 1811-1819 (1991), Journal of Biological Chemistry, volume 267, pages 11753-11759 (1992) and elsewhere. Furthermore, Journal of Biological Chemistry, volume 267, pages 22837-22842 (1992) teaches a method in which a low-molecular renin inhibitor is brought into combination with the renin-active portion of the prorenin buried in the deep groove of the three-dimensional structure to convert the same into the open type so that an antibody capable of recognizing the vicinity of the active portion of the completely matured renin is enabled to combine.
Although many reports are available on the subject matter of formation of an immunocomplex when the anti-intermediate-portion and anti-C-terminal peptide antibodies of the prorenin profragment are bound with prorenin, none of the reports are suggestive of the enzymatic activity exhibited thereby.